Latest MS Research News

Background

Many small molecules in the body are exquisitely sensitive to the
presence of a disease. These molecules, which can include DNA,
proteins, carbohydrates and fats, can be used as signatures to
quickly and accurately detect a disease and to measure its
progress or its response to a particular treatment. These
“biomarkers” (short for biological markers)
are found throughout the human body and can be measured by blood
testing, tissue biopsies and advanced imaging techniques.

As multiple sclerosis (MS) manifests in a variety of different
ways, there is a real need to gauge the disorder on a
case-by-case basis – its type, aggressiveness and progression. In
particular, identifying biomarkers for neurodegeneration – the process by which
nerve cells and fibres become damaged and lead to irreversible
disability – would be invaluable for monitoring disease
progression and assessing responses to treatment. Biomarkers are
perfectly suited to the task, as they provide a unique molecular
signature with the potential to reflect how progressive MS
evolves over time. To this end, a group of researchers including
MS Society-funded postdoctoral fellow Dr. Erin MacMillan
used an advanced diagnostic imaging technique to discover
biomarkers of secondary progressive MS. Their findings were
published in the Multiple Sclerosis Journal.

The Study

The authors used a non-invasive diagnostic imaging test,
called magnetic resonance spectroscopy (MRS), to
assess chemical changes in the brains of 46 participants with
secondary progressive MS. MRS uses the same technology as
magnetic resonance imaging (MRI). However, where MRI is set to
generate anatomical images of the brain, MRS analyzes chemicals
within the brain.

MRS scans were conducted once a year over a two-year period. The
scans measured the concentrations of various molecules in
a myelin-rich region of the brain. The
researchers followed and compared concentrations of these
molecules over the two-year period, looking for any changes over
time. They also explored whether there was a correlation between
concentrations of the molecules and participant brain size
(assessed by MRI) and disability score (assessed using both
the Expanded Disability Status Score and Multiple
Sclerosis Functional Composite scale) over the two years.

Results

The concentrations of two molecules, glutamate and glutamine,
decreased in the brain over the two-year period; glutamate fell
an average of 4.2% per year, while glutamine fell an average of
7.3% per year as measured by MRS.

There was no change in disability score, and only a very minor
decrease in brain size over time. There was no correlation
between the participants’ brain size/disability scores and the
fall in glutamate/glutamine concentrations.

Comment

The authors identified two brain molecules, glutamate and
glutamine, as potential biomarkers for secondary progressive MS.
Glutamate is a neurotransmitter; a type of chemical messenger
that communicates signals between nerve cells. Glutamine is a
by-product of glutamate that is collected and formed by
supporting cells following the release of glutamate from nerve
endings. The decline in the levels of these molecules, as noted
by the authors, could mark continuing neurodegeneration in
secondary progressive MS. Coupled with their high rate of decline
year by year – much higher than either disability scores
(none) or brain size (very minor) – the authors suggest that
glutamate and glutamine offer a sensitive and specific measure of
MS progression. This is a promising initial study and, as the
authors conclude, with further research and validation, these
biomarkers could one day be used in the clinic to monitor
individuals with progressive MS and as an outcome measure to
assess the response to a particular therapeutic.